Obesity attenuates the effect of sleep apnea on active TGF-ß1 levels and tumor aggressiveness in patients with melanoma

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2020
Author
Cubillos‑Zapata, Carolina
Martínez‑García, Miguel Ángel
Díaz‑García, Elena
Jaureguizar, Ana
Campos‑Rodríguez, Francisco
Sánchez de la Torre, Manuel
Nagore, Eduardo
Martorell‑Calatayud, Antonio
Hernández Blasco, Luis
Pastor, Esther
Abad-Capa, Jorge
Montserrat, Josep Maria
Cabriada‑Nuño, Valentín
Cano‑Pumarega, Irene
Corral-Peñafiel, Jaime
Arias, Eva
Mediano, Olga
Somoza, María
Dalmau-Arias, Joan
Almendros, Isaac
Farré, Ramon
López‑Collazo, Eduardo
Gozal, David
García Río, Francisco
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Cubillos‑Zapata, Carolina; Martínez‑García, Miguel Ángel; Díaz‑García, Elena; Jaureguizar, Ana; Campos‑Rodríguez, Francisco; Sánchez de la Torre, Manuel; ... García Río, Francisco. (2020) . Obesity attenuates the effect of sleep apnea on active TGF-ß1 levels and tumor aggressiveness in patients with melanoma. Scientific Reports, 2020, vol. 10, núm. 15528. https://doi.org/10.1038/s41598-020-72481-x.
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Abstract
Active transforming growth factor-β1 (TGF-β1), a cytokine partially regulated by hypoxia and obesity, has been related with poor prognosis in several tumors. We determine whether obstructive sleep apnea (OSA) increases serum levels of active TGF-β1 in patients with cutaneous melanoma (CM), assess their relationship with melanoma aggressiveness and analyze the factors related to TGF-β1 levels in obese and non-obese OSA patients. In a multicenter observational study, 290 patients with CM were underwent sleep studies. TGF-β1 was increased in moderate-severe OSA patients vs. non-OSA or mild OSA patients with CM. In OSA patients, TGF-β1 levels correlated with mitotic index, Breslow index and melanoma growth rate, and were increased in presence of ulceration or higher Clark levels. In CM patients, OSA was associated with higher TGF-β1 levels and greater melanoma aggressiveness only in non-obese subjects. An in vitro model showed that IH-induced increases of TGF-β1 expression in melanoma cells is attenuated in the presence of high leptin levels. In conclusion, TGF-β1 levels are associated with melanoma aggressiveness in CM patients and increased in moderate-severe OSA. Moreover, in non-obese patients with OSA, TGF-β1 levels correlate with OSA severity and leptin levels, whereas only associate with leptin levels in obese OSA patients.
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http://hdl.handle.net/10459.1/69605
DOI
https://doi.org/10.1038/s41598-020-72481-x
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Scientific Reports, 2020, vol. 10, núm. 15528
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cc-by (c) Cubillos‑Zapata, Carolina et al., 2020
Except where otherwise noted, this item's license is described as cc-by (c) Cubillos‑Zapata, Carolina et al., 2020